RESEARC H ARTIC LE Open Access
Difference between pre-operative and
cardiopulmonary bypass mean arterial pressure is
independently associated with early cardiac
surgery-associated acute kidney injury
Hussein D Kanji
1
, Costas J Schulze
1,2
, Marilou Hervas-Malo
3
, Peter Wang
1
, David B Ross
1,2
, Mohamad Zibdawi
1,2,4
,
Sean M Bagshaw
2,3,4*
Abstract
Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) contributes to increased morbidity and
mortality. However, its pathophysi ology remains incompletely understood. We hypothesized that intra-operative
mean arterial pressure (MAP) relative to pre-ope rative MAP would be an important predisposing factor for CSA-AKI.
Methods: We performed a prospective observational study of 157 consecutive high-risk patients undergoing
cardiac surgery with cardiopulmonary bypass (CPB). The primary exposure was delta MAP, defined as the pre-
operative MAP minus average MAP during CPB. Secondary exposure was CPB flow. The primary outcome was early
CSA-AKI, defined by a minimum RIFLE class - RISK. Univariate and multivariate logistic regression were performed
to explore for association between delta MAP and CSA-AKI.
Results: Mean (± SD) age was 65.9 ± 14.7 years, 70.1% were male, 47.8% had isolated coronary bypass graf t
(CABG) surgery, 24.2% had isolated valve surgery and 16.6% had combined procedures. Mean (± SD) pre-operative,

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton,
Canada
Full list of author information is available at the end of the article
Kanji et al. Journal of Cardiothoracic Surgery 2010, 5:71
/>© 2010 Kanji et al; licensee BioMed Centra l Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License ( ), which permits unrestrict ed use, distribution, and reproduction in
any medium, provided the original work is properly cited.
prolonged aortic cross clamp and CBP duration have
been found to predict CSA-AKI [9,10]. In general, how-
ever, t here is a paucity of data that has focused on the
association between specific intra-operative CPB para-
meters and risk of CSA-AKI [11].
Accordingly, we performed a prospective observational
study of patients undergoing cardiac surgery with CPB
at high-risk for CSA-AKI. Our objective was to evaluate
for associations between intra-operative CPB parameters
and early post-operative CSA-AKI. Specifically, we
examined the effect of: 1) delta mean arterial pressure
(MAP); and 2) CPB flow on the risk for early post-
operative CSA-AKI.
Methods
Study Design
This was a prospective observational cohort study. Con-
secutive patients undergoing c ardiac surgery with CPB
at the Mazankowski Alberta Hea rt Institute, Univ ersity
of Alberta Hospital in Edmonton, Canada between July
1, 2008 and October 31, 2008 were screened for enroll-
ment. The cardiac surgery program has eight surgeons
who perf orm approximatel y 140 0 open heart cases with
CPB per year. The Health Research Ethics Board at the

surgery. The rationale for this “early” definition was to
capture AKI most likely attributable to intra-operative
factors such as C PB, rather than factors in the post-
operative period. Delta MAP was defined as baseline
MAP (acquired from three independent pre-operative
blood pressure readings) minus the average MAP on
CPB (calculated as t he average of MAP readings at
15 minute intervals during CPB).
Study Protocol
For those patients enrolled, detailed data collection was
performed. All data were extracted using standardized
case-report forms and entered into a central Acc ess
2003 dat abase (Microsoft Corp, Richmond, USA). Data
extracted included: demographics (e.g. age, sex, pre-
morbid illness, pre-operative medications), pre-operative
kidney function, s urgical details (e.g. coronary bypass,
value replacement, technique, cross-clamp time), intra-
operative parameters (e.g. mean perfusion pressure,
flow, concomitant ultrafiltration, temperature, hemato-
crit, transfusions, use of vasoactive medication, use of
anti-fibrinolytics) and post-operative details (e.g. clinical,
physiologic and laboratory data). Data were also ascer-
tained on clinical outcomes including: occurrence of
AKI, receipt of RRT, duration of mechanical ventilation,
lengths of stay and hospital mortality. Postoperative data
was collected for 5 days. Pre-operative MAP was calcu-
lated as an average of three distinct measurements of
blood pressure separated by greater than 24 hours
between readings. Two of the measurements w ere con-
ducted preoperatively using an automated blood-pres-

to keep the surgical field bloodless and to avoid severe
hypotension <50 mmHg. In general the targeted MAP
was 60 mmHg. To maintain the filling volume of the
extracorporeal circuit, colloids (Pentaspan®) and Ringer’s
Lactate solution were added. When the hemoglobin was
less than 70 g/L, packed red blood cells were transfused.
Blood cardioplegia with modified Buckberg solution at a
ratio of 4:1 with high potassiu m (20 mmol/L) at induc-
tion, and at a ratio of 16:1 with low potassium (8 mmol/
L) for maintenance was used for myocardial protection.
Cardioplegic solution was delivered in an antegrade
fashion via the aortic root or by direct cannulation of
thecoronaryostiaorinaretrogradefashionviathe
coronary sinus. Heparin was reversed with protamine
following decannulation.
Patients were transferred to the cardiovascular surgical
intensive care unit post-op era tively. All fluid, inotropes,
hemodynamics and lab values including creatinine were
recorded for 5 days post-operatively. Post-operative
patient management included radial a rterial pressure
monitoring and in some cases thermodilution pulmon-
ary ar tery catheters (Baxter Healthcare Corp, Santa Ana,
USA) to measure cardiac index. Patients were extubated
from mechanical ventilation a t the discretion of the
intensivist according to standard weaning protocols. All
procedure specific data is reported on Table 1.
Statistical Analysis
The primary ou tcome w as incidence of CSA-AKI,
defined by fulfillment of a minimum RIFLE class -
RISK. Patient demographic, clinical, physiologic and

higher mean body mass index (BMI) than in the non-
AKI group (31.5 vs. 26.3, p < 0.0001). There was no sig-
nificant difference in preoperative medications, including
operative day administration, between the two groups.
Delta MAP, CPB Flow and CSA-AKI
A summary of intra-operative parameters stratified by
AKI are presented in Table 2. No pa tient received apro-
tinin. By univar iate analysis, average delta MAP was not
significantly different between AKI and non-AKI groups
(28.0 ± 13.2 mmHg vs. 31.3 ± 13.8 m mHg, p = 0.10).
However, in multivariate analysis, expressin g delta MAP
as a continuous v ariable, every one percent increase in
delta MAP, significantly increased the odds of AKI
increased by 3% after adjustment of other covariates
(OR 1.03, 1.0-1.07, p = 0.05, C-statistic = 0.783). More-
over, for patients with a delta MAP ≥26 mmHg, there
was a 2.1-fold (95% CI, 1.1-4.2, p = 0.024) increased
odds for CSA-AKI (Table 3). A delta MAP ≥26 mmHg
was found to be independently associated with CSA-
AKI in multi-variable analysis (OR 2.8; 95% CI, 1.3-6.1,
p = 0.009, Table 4).
A higher CPB flow rate was associat ed with lower odds
of CSA-AKI. Univariate analysis demonstrated that CPB
flow in the non-AKI group was significantly higher (60.9
ml/kg/min vs. 5 5.5 ml/kg/min, OR 0.2; 95% CI, 0.1-0.5,
p < 0.01) (Tables 2 and 3). By multivariable analysis, an
average blood flow on CPB is ≥54 ml/kg/min was asso-
ciated with a significantly lower odds of CSA-AKI (OR
0.3; 95% CI, 0.1-0.7, p = 0.004, Table 4). In addition, in
this model, both a BMI ≥25 kg/m

65)
p-
value
Age (years) (mean[± SD]) 64.7 ± 15.8 67.5 ± 13 0.33
Male Sex (%) 64 (69.6) 46 (70.8) 0.87
BMI (kg/m
2
) (mean[± SD]) 26.3 ± 4.1 31.5 ± 7.1 <
0.0001
CAD (%) 42 (45.7) 38 (58.5) 0.11
Angina (%) 8 (8.7) 5 (7.7) 0.83
Previous MI 35 (38) 31 (47.7) 0.23
Previous Revascularization (%) 9 (9.8) 4 (6.2) 0.42
Valve disease (%) 52 (56.5) 27 (41.5) 0.06
HTN (%) 51 (55.4) 44 (67.7) 0.12
DM - Insulin-Dependent (%) 8 (8.7) 14 (21.5) 0.02
DM - Non Insulin Dependent
(%)
23 (25) 24 (36.9) 0.12
Dyslipidemia (%) 57 (62) 48 (73) 0.12
PVD (%) 9 (9.8) 11 (16.9) 0.19
CVD (%) 9 (9.8) 5 (7.7) 0.65
Creatinine (μmol/L) (mean[±
SD])
102.1 ± 29.3 100.3 ±
24.1
0.98
Chronic Kidney Disease (%) 12 (13) 9 (13.8) 0.88
Pre-op SBP (mm Hg) (mean [±
SD])

Post-operative o utcomes, including time o n mechanical
ventilation, length of ICU stay were similar between
those with and without CSA-AKI (Table 5). No patient
rec eived acute RRT and all patients survived to hospital
discharge.
Discussion
We performed a prospective observational study of 157
cardiac surgery patients receiving cardiopulmonary
bypass at eleva ted risk for CSA-AKI to evaluate the
impact of intra-operative variables, specifically delta
MAP and CPB flow, on the development of early post-
operative CSA-AKI.
We found early post-operative AKI was common,
occurring in 41% of patients. While this would appear
significantly higher than prior studies, our study was
focused on patients at higher risk for CSA-AKI. In two
observational studies of CSA-AKI, defined by the RIFLE
criteria, the post-operative incidence of CSA-AKI ranged
3.7-9%(16, 17). In addition, we found that a delta MAP
≥26 mmHg was independently associated with develop-
ment of early CSA-AKI. More specifical ly, every 1%
increase in delta MAP was found to be associated with
a3%higherriskofCSA-AKI.WefoundthatCPB
Table 2 Summary of intra-operative variables stratified by post-operative CSA-AKI
Variable No AKI (n = 92) AKI (n = 65) p-value
Valve only surgery (%) 26 (28.3) 12 (18.5) 0.16
Combined (valve + CABG) (%) 43 (46.7) 21 (32.3) 0.07
Re-operation (%) 8 (8.7) 6 (9.2) 0.91
# Grafts (mean [± SD]) 3.4 ± 1.1 3.5 ± 1.1 0.77
Duration of CPB (min, mean [± SD]) 126.6 ± 52 127.2 ± 63.2 0.69

BMI ≥25 kg/m
2
(present) 4.4 1.9-10.2 0.0007
Valve disease (present) 0.55 0.3-1.0 0.06
DM (present) 2.2 1.1-4.2 0.025
PVD (present) 1.9 0.9-3.3 0.19
HTN (present) 1.7 0.9-3.3 0.12
Delta MAP (per 1 mmHg) 1.02 0.99-
1.04
0.14
Delta MAP ≥26 mmHg (present) 2.1 1.1-4.2 0.024
Flow ≥54 per mL/kg/min (present) 0.2 0.1-0.5 0.0002
pH 1.4 0.8-2.7 0.26
Pre-operative ACE inhibitor (present) 0.6 0.3-1.1 0.1
Valve Surgery (present) 0.5 0.3-1 0.07
Peak CPB-MAP 0.5 0.2-0.97 0.04
Pre-operative Systolic BP (≥111
mmHg)
2.1 0.99-4.6 0.05
Duration of CPB MAP ≤60 (per 1 min) 1.99 0.9-4.4 0.89
Abbreviations: BMI = Body Mass Index; DM = Diabetes Mellitus PVD =
Peripheral Vascular Disease; HTN = Hypertension; MAP = Mean Arterial
Pressure; ACE = Angiotensin Converting Enzyme; CPB=Cardiopulmonary
Bypass’ MAP = mean arterial pressure
Kanji et al. Journal of Cardiothoracic Surgery 2010, 5:71
/>Page 5 of 9
circuit flow <54 mL/kg/min was independently asso-
ciated with higher risk of early post-operative AKI. We
also found that higher BMI (> 25 kg/m
2

baseline blood pressure is associated 2.8 times greater
risk for the development of CSA-AKI. An absolute pro-
longed drop in pressure <60 mmHg has previously been
identified as risk factor for CSA-AKI [7,19]. Further-
more, poorer neurological outcomes and end-organ per-
fusion have been associated with CPB pressures <60
mm Hg [20]. The role of relative hypotension during
CPB remains debated and da ta exists to sugge st that
absolute hypotension while on CPB alone is not asso-
ciated with the development of CSA-AKI [21]. Despite
the ongoing discussion on role of perfusion pressure,
there is a convincing data to suggest that increased CPB
duration has deleterious effects on kidney function and
prom otes injury [1,10,22]. Unfortunately the majority of
the studies that report on CPB duration did not include
CPB hemodynamics, specifically CPB-MAP, in the ana-
lysis and none of the studies evaluate the change relative
to pre-operative pre ssures (i.e. delta MAP) [1,22]. We
Table 4 Multi-variable adjusted logistic regression
model
¶
of association between delta MAP and CSA-AKI
Parameter Odds Ratio 95% CI P-value
Male sex 0.7 0.3-1.7 0.49
Age ≥75 years (present) 2.1 0.9-4.9 0.08
BMI ≥25 kg/m
2
(present) 4.2 1.6-11.2 0.0039
Delta MAP ≥26 mmHg (present) 2.8 1.3-6.1 0.009
Flow ≥54 per mL/kg/min (present) 0.3 0.1-0.7 0.004

20% [23]. A recent study by Aronson et al demonstrated
that pre-operative hypertension with an increase in
pulse pressure is an independent risk factor for AKI
[24]. Our study would ar gue that hyperte nsion might be
a surrogate marker for a greater relative drop in CPB
MAP, which might contribute to CSA-AKI.
The literature has examples of studies that refute CPB
hypotension as an independent risk factor for CSA-AKI,
however, these studies are generally small, observational,
underpowered, and more importantly, these studies
failed to investigate the impact of hypotension as a func-
tion of pre-operative baseline MAP [20,25-27]. The
notion of relative hypotension or delta-MAP induced
end-organ injury has been recently shown. Gottesman et
al found that patients with greater drops o f MAP on
CPB relativ e to pre-operative MAP had poorer neurolo-
gical outcomes [28]. Furthermore, Lombardi et al
demonstrated that lower MAP duri ng CPB was an inde-
pendent risk factor in the develo pment of CSA-AKI [8].
This study suggest ed low CPB MAP is a potential ly
important determinant for CSA-AKI, however, does not
correlate duration of hypotension to pre-operative base-
line. In addition, the study showed a difference of only
0.5 mmHg between cohorts, which though statistically
different, may h ave limited clini cal relevance. Though
Lomabrdi et al suggest that hypotension during CPB in
general could have deleterious effect on post-operative
kidney function, our study has shown that the magni-
tude of injury may be more a function of the degree of
hypotension relative to pre-operative baseline MAP.

theoretically reduce renal perfusion) or by increasing
CBP flow. As we found the latter to also be p rotective
against CSA-AKI, we would suggest that this b e consid-
ered first; however, we also caution that confirmatory
studies are needed.
Our study has notable limitations. Firstly, our study is
single centered, relatively small and observational in nat-
ure making it prone to bias. Not being able to control
for interventions may have resulted in patients who
were deemed high-risk to be maintained intra-opera-
tively at a higher MAP. Secondly, our study may have
been subjected to a selection bias, for example a certain
surgeon may be more apt to operate on more compli-
cated and higher risk patients with different intra-opera-
tive practices. Thirdly, the small sample and relatively
sensitive definition f or AKI used in our study, coupled
with a short post-operative study period, largely limited
our statistical power and precluded us from detecting
potentially meaningful differences in clinical outcomes,
such as duration of mechanical ventilation, duration of
ICUstayandneedforRRT.Asaforementioned,this
was in part intended, in order to isolate as best as possi-
ble the impact of intra-operative hemodynamic variables
on risk of post -operative CSA-AKI. We attempted to
control for available confounders by applying an a priori
selection criteria and collection of fa ctors that could
contribute to CSA-AKI. These factors were included in
multivariable analysis. Finally, we recognize for the
aforementioned reasons, our single-centre study of
patients undergoing cardiac surgery with CPB at higher

of Alberta, Edmonton, Canada.
3
Epidemiology Coordinating and Research
Centre (EPICORE), University of Alberta, Edmonton, Canada.
4
Division of
Critical Care Medicine, Faculty of Medicine and Dentistry, University of
Alberta, Edmonton, Canada.
Authors’ contributions
HK developed study protocol, obtained data, analyzed data and wrote
manuscript. CS obtained data and provided critical revision of manuscript.
PW obtained data. DR and MZ developed the study protocol and provided
critical revision of the manuscript. MH analyzed data. SMB conceived the
study, developed study protocol, analyzed data and provided critical revision
of the manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 7 May 2010 Accepted: 8 September 2010
Published: 8 September 2010
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doi:10.1186/1749-8090-5-71
Cite this article as: Kanji et al.: Difference between pre-operative and
cardiopulmonary bypass mean arterial pressure is independently
associated with early cardiac surgery-associated acute kidney injury.
Journal of Cardiothoracic Surgery 2010 5:71.
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